Chemistry

Fondaparinux sodium (Arixtra, formerly Org21540/SR90107A), the first synthetic pentasaccharide anticoagulant, is prepared for injection as a decasodium salt. The chemical formula is C31H43N3Na10O49S8, and the molecular mass is 1728 Da (Arixtra Package Insert, 2006). The chemical structure is presented in Figure 5 of Chapter 7.

Fondaparinux is a methyl glycoside analogue designed and optimized based on the AT binding site of UFH. Binding to AT (1:1 stoichiometry) results in the allosteric induction of an irreversible conformational change in AT. This AT conformer exhibits high binding affinity for factor Xa, preventing thrombin generation (Arocas et al., 2001). After covalent binding of Xa to AT, fondaparinux is released without structural alteration, allowing subsequent binding once again to free AT. Unlike UFH and (longer fragments within) low molecular weight heparin (LMWH), binding of fondaparinux to AT does not facilitate inhibition of factor IIa, due to the structural absence of the heparin thrombin-binding domain.

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